The RCCX theory explains a genetic mutation which may be the genetic predisposition for some people who develop ME. I know for certain my story fits with this theory and a lot of others as well. To put it simply, it is a mutation in the:
There is a part of the genome, nestled among the immune system genes called the RCCX module. This module breaks the rules of genetics in that it mutates often (even between generations) and it allows contiguous (side-by-side) gene mutations to be co-inherited at a very high rate, meaning that it allows for several “rare” genetic conditions to be found in one individual.
RP1: function unknown
TNXB: codes for tenascin X, a protein found in the extracellular matrix of collagen
C4 :codes for a protein involved in the complement system of the immune system
CYP21A2: codes for the key enzyme, 21hydroxylase, which is involved in the acute stress response. 21hydroxylase helps to make cortisol from 17 hydroxyprogesterone and aldosterone.
sometimes carriers with one good gene and one non-functional mutated gene or homozygotes with 2 partially functioning mutated genes for an enzyme (e.g. 21 hydroxylase) mutation can get into trouble clinically if the body suddenly faces a higher than normal demand for the enzyme. Again, when this happens, the ingredients/precursors (e.g. progesterone, cholesterol) build up and get shunted onto other pathways (into androgens-male hormones and a small amount into estrogens) and the products become deficient (e.g. cortisol and aldosterone). This sets into effect a whole host of clinical syndromes-those due to high precursors/shunted products (e.g. high progesterone, androgens, cholesterol), those due to low products (e.g. low cortisol, low aldosterone). A word about the "low cortisol". There is quite a bit of clinical evidence that the high acute stress response (high stress cortisol) remains until the end (until "the wall is hit" as I call it), but basal cortisol trends downward as he person becomes chronically ill. a significant stressor or prolonged stress with all of the symptoms/syndromes which can be caused by the associated enzyme, 21hydroxylase becoming overwhelmed occurs. The stress of this endocrine and inflammatory cascade could certainly turn on CDR resulting in the mitochondrial shutdown recently demonstrated in severe CFS/ME.
There is a part of the genome, nestled among the immune system genes called the RCCX module. This module breaks the rules of genetics in that it mutates often (even between generations) and it allows contiguous (side-by-side) gene mutations to be co-inherited at a very high rate, meaning that it allows for several “rare” genetic conditions to be found in one individual.
RP1: function unknown
TNXB: codes for tenascin X, a protein found in the extracellular matrix of collagen
- Mutations sometimes associated with EDS
- Mutations often associated with joint hypermobility NOT meeting criteria for EDS
- Mutations possibly associated with stiff or even normal-seeming tissues depending on the mutation,
- Mutations have been associated with TGF beta abnormalities implicated in fibrosis
C4 :codes for a protein involved in the complement system of the immune system
- Mutations implicated in autoimmune diseases, immunodeficiency/CVID, schizophrenia
CYP21A2: codes for the key enzyme, 21hydroxylase, which is involved in the acute stress response. 21hydroxylase helps to make cortisol from 17 hydroxyprogesterone and aldosterone.
- Mutations result in an exaggerated stress response (high acute stress response cortisol), low basal cortisol and elevated CRH (corticotropin releasing hormone, aka CRF) which directly turns on the immune system and inflammation.
- Carriers of CYP21A2 mutations have BOTH an exaggerated stress response AND are at risk for 21 hydroxylase failure resulting in inability to make cortisol and aldosterone with subsequent 17 hydroxyprogesterone and androgen build up. Called "21hydroxylase overwhelm" going forward. This is a stress-vulnerable switch which can result in severe chronic illness if flipped.
sometimes carriers with one good gene and one non-functional mutated gene or homozygotes with 2 partially functioning mutated genes for an enzyme (e.g. 21 hydroxylase) mutation can get into trouble clinically if the body suddenly faces a higher than normal demand for the enzyme. Again, when this happens, the ingredients/precursors (e.g. progesterone, cholesterol) build up and get shunted onto other pathways (into androgens-male hormones and a small amount into estrogens) and the products become deficient (e.g. cortisol and aldosterone). This sets into effect a whole host of clinical syndromes-those due to high precursors/shunted products (e.g. high progesterone, androgens, cholesterol), those due to low products (e.g. low cortisol, low aldosterone). A word about the "low cortisol". There is quite a bit of clinical evidence that the high acute stress response (high stress cortisol) remains until the end (until "the wall is hit" as I call it), but basal cortisol trends downward as he person becomes chronically ill. a significant stressor or prolonged stress with all of the symptoms/syndromes which can be caused by the associated enzyme, 21hydroxylase becoming overwhelmed occurs. The stress of this endocrine and inflammatory cascade could certainly turn on CDR resulting in the mitochondrial shutdown recently demonstrated in severe CFS/ME.
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